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Catalytic Hydrogenation of 5,6‐Dihydro‐4 H ‐1,2‐oxazines Bearing a Functionalized Methylene Group at C‐3
Author(s) -
Sukhorukov Alexey Yu.,
Lesiv Alexey V.,
Eliseev Oleg L.,
Khomutova Yulia A.,
Ioffe Sema L.,
Borissova Alexandra O.
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200800288
Subject(s) - chemistry , substituent , catalytic hydrogenation , catalysis , alkoxy group , acetic acid , methylene , medicinal chemistry , pyrrolidine , methanol , organic chemistry , noyori asymmetric hydrogenation , bond cleavage , enantioselective synthesis , alkyl
The catalytic hydrogenation of readily available methyl 2‐(5,6‐dihydro‐4 H ‐1,2‐oxazin‐3‐yl)acetates 6 has been studied. Dihydrooxazines 6 without an alkoxy substituent at C‐6 under mild hydrogenation conditions in methanol produce a dynamic mixture of enamines 7 and tetrahydro‐2‐furanamines 7′ (α + β). These products can be transformed into 1,4‐amino alcohols 8 under more robust hydrogenation conditions or into isomeric dihydrofurans 9 and 10 if the reduction is carried out in glacial acetic acid. Reduction of dihydrooxazines 6h , i , which possess an alkoxy substituent at C‐6, under similar conditions affords pyrrolidine derivatives 12 , 13 and 14 . A general mechanistic scheme for the hydrogenation reaction that involves an initial N–O bond cleavage has been suggested. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)